Effects of targeted disruption of the mouse angiotensin II type 2 receptor gene on stress-induced hyperthermia

Abstract

1. We have previously reported that brain angiotensin II type 2 receptors (AT2) contribute to immunological stress-induced hyperthermia (fever) in rats. Now, in mice, we report the effect of AT2 gene disruption on the hyperthermia induced by immunological (interleukin-1 (IL-1) injection) and non-immunological (saline injection or cage switch) stress. 2. AT2-deficient and control mice both showed typical circadian rhythmicity in body temperature and physical activity. During the latter half of the dark period, AT2-deficient mice exhibited a lower body temperature than the controls. 3. By comparison with the controls, AT2-deficient mice exhibited: (i) a significantly smaller hyperthermia after intraperitoneal (i.p.) injection of IL-1beta; (ii) significantly greater increases in body temperature and physical activity after i. p. saline; and (iii) a significantly greater hyperthermia (but a similar increase in activity) during cage-switch stress. 4. These results suggest that AT2, presumably in the brain, plays important roles in stress-induced hyperthermia in mice.

Figure 1. Diurnal changes in body temperature and physical activity in control and AT2-deficient mice

Mean changes in resting body temperature (A) and physical activity (B) in control and AT2-deficient mice over a 5 day period. The bars at the top of each panel indicate the periods of darkness. Each parameter was measured at 30 min intervals and the data for each group are presented as mean values.

Figure 2. Body temperature and behavioural responses induced in control and AT2-deficient mice by intraperitoneal injection of interleukin-1 (IL-1)

Mean values (±s.e.m.) obtained for body temperature (A) and physical activity (B) in control and AT2-deficient mice after i.p. injection of IL-1β (10 μg kg⁻¹). Each parameter was measured at 5 min intervals.

Figure 4. Body temperature and behavioural responses induced in control and AT2-deficient mice by cage- switch stress

Mean values (±s.e.m.) obtained for body temperature (A) and physical activity (B) in control and AT2-deficient mice during exposure to cage-switch stress. Each parameter was measured at 5 min intervals.

Figure 3. Body temperature and behavioural responses induced in control and AT2-deficient mice by intraperitoneal injection of saline

Mean values (±s.e.m.) obtained for body temperature (A) and physical activity (B) in control and AT2-deficient mice after i.p. injection of saline (1 ml kg⁻¹). Each parameter was measured at 5 min intervals.